In the course of an attempt to develop a single GC/MS assay for chlorpromazine (CPZ) and 13 of its metabolites, it was observed that some of the metabolites thermally decompose to produce varying amounts of artifactual CPZ depending upon the instrumental conditions. For example, CPZ sulfoxide and CPZ N-oxide which usually accompany CPZ in extracts of various biological fluids, are particularly susceptible to pyrolysis in the GC. Therefore we propose to conduct a systematic investigation of the influence of relevant experimental parameters --e.g., temperature of the GC flash vaporizer, detector temperature, column configuration, reactions of derivatizing reagents with metabolites other than the ones they are intended to attack, etc. -- in order to establish the set of experimental conditions that minimize this type of analytical artifact. To further improve the reliability of the quantitation of CPZ, a ring-deuterated CPZ will be evaluated as an internal standard. Using GC/MS, the optimized protocol (including the use of the isotopically labeled internal standard) will be applied to a statistically significant number of specimens that will be spiked with all of the anticipated CPZ metabolites at realistic levels in order to test its performance.